NONSTEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDS) ASSOCIATE WITH ZWITTERIONIC PHOSPHOLIPIDS - INSIGHT INTO THE MECHANISM AND REVERSAL OF NSAID-INDUCED GASTROINTESTINAL INJURY

The molecular basis of the injurious actions of non-steroidal anti-inf lammatory drugs (NSAIDs) on the gastrointestinal (GI) tract is only pa rtly understood. In this study we have obtained evidence, employing bo th in vitro and in vivo systems, that five NSAIDs have the ability to form a chemical association with zwitterionic phospholipids. Since thi s same class of phospholipids line the luminal aspects of the mucus ge l layer to provide it with non-wettable properties, this intermolecula r association may be the mechanism by which NSAIDs attenuate the hydro phobic barrier properties of the upper GI tract. Preassociating a numb er of NSAIDs with exogenous zwitterionic phospholipids prevented this increase in surface wettability of the mucus gel layer and protected r ats against the injurious GI side-effects of these drugs, while enhanc ing their lipid permeability, antipyretic and anti-inflammatory activi ty.